{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 462263142 | IUPAC_name = (8''S'',13''S'',14''S'',17''R'')-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,14,15,16-octahydrocyclopenta[''a'']phenanthren-3-one | image = Norgestrienone.svg | image_class = skin-invert-image | width = 225px

<!--Clinical data--> | tradename = Ogyline, Planor, Miniplanor | pregnancy_category = | legal_status = | routes_of_administration = By mouth | class = Progestogen; Progestin; Androgen; Anabolic steroid

<!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =

<!--Identifiers--> | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 848-21-5 | ATC_prefix = G03 | ATC_suffix = AC07 | PubChem = 13313 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 12749 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 89386PYU9O | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07220 | synonyms = RU-2010; A-301; 17α-Ethynyltrienolone; 17α-Ethynyltrenbolone; Δ<sup>9,11</sup>-Norethisterone; 17α-Ethynylestra-4,9,11-trien-17β-ol-3-one

<!--Chemical data--> | C=20 | H=22 | O=2 | SMILES = O=C4\C=C3/C(=C2/C=C\[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)C)CC4 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C20H22O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,8,10,12,17-18,22H,4-7,9,11H2,2H3/t17-,18+,19+,20+/m1/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = GVDMJXQHPUYPHP-FYQPLNBISA-N }} <!-- Definition and medical uses --> '''Norgestrienone''', sold under the brand names '''Ogyline''', '''Planor''', and '''Miniplanor''', is a progestin medication which has been used in birth control pills, sometimes in combination with ethinylestradiol.<ref name="Elks2014">{{cite book | vauthors = Elks J | title = The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA887|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=887–}}</ref><ref name="MortonHall2012">{{cite book | vauthors = Morton IK, Hall JM | title = Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA202|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=202–}}</ref><ref name="DiazPavez1978">{{cite journal | vauthors = Diaz S, Pavez M, Quinteros E, Diaz J, Robertson DN, Croxatto HB | title = Clinical trial with subdermal implants containing norgestrienone | journal = Contraception | volume = 18 | issue = 4 | pages = 429–440 | date = October 1978 | pmid = 720075 | doi = 10.1016/0010-7824(78)90027-6 }}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA751|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=751–}}</ref><ref name="Martindale">{{cite book | veditors = Sweetman SC |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |page=2122 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|chapter-url=https://www.medicinescomplete.com/|quote=Norgestrienone is a progestogen structurally related to norethisterone that has been used as an oral contraceptive. Typical doses have been 2 mg daily with an oestrogen, and 350 micrograms daily when used alone.}}</ref> It was developed by Roussel Uclaf and has been registered for use only in France.<ref name="IndexNominum2000" /><ref name="Martindale" /><ref name="McGuire2000">{{cite book | vauthors = McGuire JL | title = Pharmaceuticals, 4 Volume Set|url=https://books.google.com/books?id=uG9qAAAAMAAJ|year=2000|publisher=Wiley|isbn=978-3-527-29874-7|page=1580,1599}}</ref> Under the brand name '''Planor''', it has been marketed in France as 2&nbsp;mg norgestrienone and 50&nbsp;μg ethinylestradiol tablets.<ref name="HumansOrganization2007">{{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=World Health Organization|author3=International Agency for Research on Cancer|title=Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy|url=https://books.google.com/books?id=aGDU5xibtNgC&pg=PA455|year=2007|publisher=World Health Organization|isbn=978-92-832-1291-1|pages=455–}}</ref> It is taken by mouth.<ref name="Martindale" />

<!-- Side effects and mechanism --> Norgestrienone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.<ref name="pmid1291626" /> It has some androgenic activity.<ref name="Axelrod1982" /><ref name="LauritzenStudd2005" /><ref name="GiulioMonosson2012" /><ref name="pmid7065053">{{cite journal | vauthors = Rozenbaum H | title = Relationships between chemical structure and biological properties of progestogens | journal = American Journal of Obstetrics and Gynecology | volume = 142 | issue = 6 Pt 2 | pages = 719–724 | date = March 1982 | pmid = 7065053 | doi = 10.1016/S0002-9378(16)32477-2 }}</ref>

<!-- History, society, and culture --> Norgestrienone was first described in the literature in 1965.<ref name="LauritzenStudd2005" /> It is sometimes referred to as a "second-generation" progestin.<ref name="pmid9988833" /> Norgestrienone is no longer available.{{cn|date=June 2023}}

==Medical uses== Norgestrienone was used in hormonal contraception to prevent pregnancy.<ref name="MortonHall2012" /><ref name="HumansOrganization2007" /> It has typically been used as an oral contraceptive at a dosage of 2&nbsp;mg/day in combination with ethinylestradiol and 350&nbsp;μ/day when used alone.<ref name="Martindale" />

==Side effects== {{See also|Progestin#Side effects}}

==Pharmacology== ===Pharmacodynamics=== Norgestrienone has been found to possess similar affinity for the progesterone receptor and androgen receptor,<ref name="pmid1291626">{{cite journal | vauthors = Loughney DA, Schwender CF | title = A comparison of progestin and androgen receptor binding using the CoMFA technique | journal = Journal of Computer-Aided Molecular Design | volume = 6 | issue = 6 | pages = 569–581 | date = December 1992 | pmid = 1291626 | doi = 10.1007/bf00126215 | s2cid = 22004130 | bibcode = 1992JCAMD...6..569L }}</ref> and in accordance, has some androgenic activity.<ref name="Axelrod1982">{{cite book | vauthors = Axelrod J | title = Biochemical Actions of Hormones|url=https://books.google.com/books?id=AxpPAQAAIAAJ|date=1 January 1982|publisher=Academic Press|isbn=978-0-12-452809-3}}</ref><ref name="LauritzenStudd2005">{{cite book | vauthors = Lauritzen C, Studd JW | title = Current Management of the Menopause|url=https://books.google.com/books?id=WD7S7677xUUC&pg=PA45|date=22 June 2005|publisher=CRC Press|isbn=978-0-203-48612-2|pages=45–}}</ref><ref name="GiulioMonosson2012">{{cite book | vauthors = Di Giulio RT, Monosson E | title = Interconnections Between Human and Ecosystem Health | url = https://books.google.com/books?id=dQ1JCAAAQBAJ&pg=PA60 |date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-1523-7|pages=60–}}</ref><ref name="pmid7065053" /> The androgenic activity of norgestrienone is greater than that of other 19-nortestosterone derivatives due to the presence of the C9(11) double bond, which enhances said activity.<ref name="pmid7065053" /> The ratio of progestogenic to androgenic activity appears to be much lower for norgestrienone that it is for other 19-nortestosterone progestins such as norethisterone and levonorgestrel.<ref name="pmid7382482" /><ref name="pmid7421203" /><ref name="pmid8136304" /><ref name="RaynaudOjasoo1979" /> Gestrinone, the 18-methyl analogue of norgestrienone, has even greater androgenic activity than norgestrienone, as this modification increases androgenic activity similarly.<ref name="pmid7065053" />

{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;" |+ class="nowrap" | Relative affinities (%) of norgestrienone and related steroids |- ! Compound || {{abbrlink|PR|Progesterone receptor}} || {{abbrlink|AR|Androgen receptor}} || {{abbrlink|ER|Estrogen receptor}} || {{abbrlink|GR|Glucocorticoid receptor}} || {{abbrlink|MR|Mineralocorticoid receptor}} || {{abbrlink|SHBG|Sex hormone-binding globulin}} || {{abbrlink|CBG|Corticosteroid binding globulin}} |- | Norethisterone || 155–156 || 43–45 || <0.1 || 2.7–2.8 || 0.2 || ? || ? |- | Norgestrienone || 63–65 || 70 || <0.1 || 11 || 1.8 || ? || ? |- | Levonorgestrel || 170 || 84–87 || <0.1 || 14 || 0.6–0.9 || ? || ? |- | Gestrinone || 75–76 || 83–85 || <0.1, 3–10 || 77 || 3.2 || ? || ? |- class="sortbottom" | colspan="9" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' Values are percentages (%). Reference ligands (100%) were progesterone for the {{abbrlink|PR|progesterone receptor}}, testosterone for the {{abbrlink|AR|androgen receptor}}, {{abbr|E2|estradiol}} for the {{abbrlink|ER|estrogen receptor}}, {{abbrlink|DEXA|dexamethasone}} for the {{abbrlink|GR|glucocorticoid receptor}}, aldosterone for the {{abbrlink|MR|mineralocorticoid receptor}}, {{abbrlink|DHT|dihydrotestosterone}} for {{abbrlink|SHBG|sex hormone-binding globulin}}, and cortisol for {{abbrlink|CBG|Corticosteroid-binding globulin}}. '''Sources:''' <ref name="pmid7382482">{{cite journal | vauthors = Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP | title = Steroid flexibility and receptor specificity | journal = Journal of Steroid Biochemistry | volume = 13 | issue = 1 | pages = 45–59 | date = January 1980 | pmid = 7382482 | doi = 10.1016/0022-4731(80)90112-0 }}</ref><ref name="pmid7421203">{{cite journal | vauthors = Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP | display-authors = 6 | title = Steroid hormone receptors and pharmacology | journal = Journal of Steroid Biochemistry | volume = 12 | pages = 143–157 | date = January 1980 | pmid = 7421203 | doi = 10.1016/0022-4731(80)90264-2 }}</ref><ref name="pmid8136304">{{cite journal | vauthors = Ojasoo T, Raynaud JP, Doé JC | title = Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 48 | issue = 1 | pages = 31–46 | date = January 1994 | pmid = 8136304 | doi = 10.1016/0960-0760(94)90248-8 | s2cid = 21336380 }}</ref><ref name="RaynaudOjasoo1979">{{cite book | vauthors = Raynaud J, Ojasoo T, Bouton M, Philibert D |title=Drug Design |year=1979 |pages=169–214 |doi=10.1016/B978-0-12-060308-4.50010-X |chapter-url= https://books.google.com/books?id=bhAlBQAAQBAJ&pg=PA169|isbn=9781483216102 |chapter=Receptor Binding as a Tool in the Development of New Bioactive Steroids|series=Medicinal Chemistry: A Series of Monographs |volume=11 |publisher=Academic Press }}</ref> |}

===Pharmacokinetics=== The metabolism of norgestrienone in humans has been studied.<ref name="Raynaud1971">{{cite journal | vauthors = Raynaud JP | title = Metabolism of contraceptive steroids in man. | journal = Excerpta Medica International Congress Series | date = 1970 | volume = 219 | pages = 915–922 | url = https://www.popline.org/node/480947 | archive-url = https://web.archive.org/web/20180329184746/https://www.popline.org/node/480947 | archive-date = 29 March 2018 }}</ref>

==Chemistry== {{See also|List of progestogens|List of androgens/anabolic steroids}}

Norgestrienone, also known as 17α-ethynyl-19-nor-δ<sup>9,11</sup>-testosterone or as 17α-ethynylestra-4,9,11-trien-17β-ol-3-one, as well as δ<sup>9,11</sup>-norethisterone or 17α-ethynyltrienolone (17α-ethynyltrenbolone), is a synthetic estrane steroid and a derivative of testosterone and 19-nortestosterone.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="LaverySanfilippo2012">{{cite book | vauthors = Lavery JP, Sanfilippo JS | title = Pediatric and Adolescent Obstetrics and Gynecology|url=https://books.google.com/books?id=l9XTBwAAQBAJ&pg=PA236|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5064-7|pages=236–}}</ref> It is structurally related to the anabolic steroid trenbolone (19-nor-δ<sup>9,11</sup>-testosterone; the non-17α-ethynylated analogue of norgestrienone), the progestogenic and androgenic steroid gestrinone (the 13β-ethyl variant or 18-methyl derivative of norgestrienone), and the anabolic steroid tetrahydrogestrinone (the 18-methyl and 17α-ethyl variant of norgestrienone).<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="GomelBrill2010">{{cite book | vauthors = Gomel V, Brill A |title= Reconstructive and Reproductive Surgery in Gynecology|url=https://books.google.com/books?id=C4TOBQAAQBAJ&pg=PA90|date=27 September 2010|publisher=CRC Press|isbn=978-1-84184-757-3|pages=90–}}</ref>

==History== Norgestrienone was first described in the literature in 1965.<ref name="LauritzenStudd2005" /> It is sometimes referred to as a "second-generation" progestin based on its time of introduction.<ref name="pmid9988833">{{cite journal | vauthors = Weiss G | title = Risk of venous thromboembolism with third-generation oral contraceptives: A review | journal = American Journal of Obstetrics and Gynecology | volume = 180 | issue = 2 Pt 2 | pages = 295–301 | date = February 1999 | pmid = 9988833 | doi = 10.1016/S0002-9378(99)70721-0 }}</ref>

==Society and culture==

===Generic names=== ''Norgestrienone'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}.<ref name="Elks2014" /><ref name="MortonHall2012" /><ref name="IndexNominum2000" /> It is also known by its developmental code names ''RU-2010'' and ''A-301''.<ref name="Elks2014" /><ref name="MortonHall2012" /><ref name="IndexNominum2000" />

===Brand names=== Norgestrienone has been marketed under the brand names Ogyline, Planor, and Miniplanor.<ref name="Elks2014" /><ref name="MortonHall2012" /><ref name="IndexNominum2000" />

===Availability=== Norgestrienone is no longer marketed and hence is no longer available in any country.{{cn|date=June 2023}} It was previously used in France.<ref name="IndexNominum2000" /> The medication was never marketed in the United States.<ref name="Lednicer2009">{{cite book| vauthors = Lednicer D |title=Strategies for Organic Drug Synthesis and Design|url=https://books.google.com/books?id=fEwl6Qev-mUC&pg=PA134|date=4 March 2009|publisher=John Wiley & Sons|isbn=978-0-470-39959-0|pages=134–}}</ref>

==Research== Norgestrienone has been studied for use in male hormonal contraception.<ref name="Scheater1978">{{cite report | vauthors = Schearer SD | title = The use of progestins and androgens as a male contraceptive. Hormonal control of male fertility. | work = DHEW Publication No.(NIH). | date = 1978 | pages = 78–1097 | url = https://www.popline.org/node/443605 | archive-url = https://web.archive.org/web/20180329184345/https://www.popline.org/node/443605 | archive-date= 29 March 2018 }}</ref>

== References == {{Reflist}}

{{Progestogens and antiprogestogens}} {{Androgens and antiandrogens}} {{Progesterone receptor modulators}} {{Androgen receptor modulators}}

Category:Abandoned drugs Category:Tertiary alcohols Category:Ethynyl compounds Category:Androgens Category:Estranes Category:Ketones Category:Progestogens